Impaired phagocytic function in CX3CR1+ tissue-resident skeletal muscle macrophages prevents muscle recovery after influenza A virus-induced pneumonia in aged mice
| Autor: | Jacob I. Sznajder, Hiam Abdala-Valencia, Emilia Lecuona, Lango Sichizya, Ziyan Lu, Satoshi Watanabe, Nikolay S. Markov, Nikita Joshi, Alexandra C. McQuattie-Pimentel, Raul Piseaux-Aillon, Lynn C. Welch, Luciano Amarelle, Kiwon Nam, Alexander V. Misharin, Yuliya Politanska, Constance E. Runyan, G. R. Scott Budinger, Masahiko Shigemura, Kinola J.N. Williams |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Cell growth business.industry Phagocytosis Skeletal muscle MERTK medicine.disease_cause 3. Good health 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Downregulation and upregulation Immunology CX3CR1 Influenza A virus medicine Receptor business 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/833236 |
| Popis: | Skeletal muscle dysfunction in survivors of pneumonia is a major cause of lasting morbidity that disproportionately affects older individuals. We found that skeletal muscle recovery was impaired in aged compared with young mice after influenza A virus-induced pneumonia. In young mice, recovery of muscle loss was associated with expansion of tissue-resident skeletal muscle macrophages and downregulation of MHC II expression, followed by a proliferation of muscle satellite cells. These findings were absent in aged mice and in mice deficient in Cx3cr1. Transcriptomic profiling of tissue-resident skeletal muscle macrophages from aged compared with young mice showed downregulation of pathways associated with phagocytosis and proteostasis, and persistent upregulation of inflammatory pathways. Consistently, skeletal muscle macrophages from aged mice failed to downregulate MHCII expression during recovery from influenza A virus induced pneumonia and showed impaired phagocytic function in vitro. Like aged animals, mice deficient in the phagocytic receptor Mertk showed no macrophage expansion, MHCII downregulation or satellite cell proliferation and failed to recover skeletal muscle function after influenza A pneumonia. Our data suggest that a loss of phagocytic function in a CX3CR1+ tissue-resident skeletal muscle macrophage population in aged mice precludes satellite cell proliferation and recovery of skeletal muscle function after influenza A pneumonia. |
| Databáze: | OpenAIRE |
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